Protein A is a constituent of the cell wall of the bacterium Staphylococcus aureus. One form has a reported molecular weight of 42,000 and is a major component (1.7% of total cell protein) of the cell wall. See Bjork, (1972) Eur. J. Biochem. 29:579. Measurements of frictional ratio and intrinsic viscosity of protein A in comparison to most globular proteins suggest that its shape is relatively elongated. Controlled trypsinization of the molecule reveals 4 homologous peptide domains (designated in order from the N-terminus as D, A, B, C), each of which can bind one molecule of IgG at the Fc region. See Sjodahl, J. (1977) Eur. J. Biochem. 73:343 and L Sjodahl, J. (1977) Eur. J. Biochem. 78:471. The relative binding efficiency of protein A is dependent upon a number of factors, including pH, species, class, and subclass of IgG. Because of its ability to bind to IgG without significantly affecting the affinity of immunoglobulin for antigen, protein A is widely used as an immunoabsorbent in a variety of diagnostic and basic research test systems. See U.S. Pat. No. 4,322,274. Recent interest in applications of protein A has centered around its possible clinical use in anti-cancer treatment. Sensitized peripheral blood lymphocytes, normally responsible for cytotoxicity of tumor cells, are hypothesized to be inhibited in this function by serum blocking factors which are presumed to consist of specific antigens, antibodies, antiglobulins, and immune complexes. See Barnes, B. C. (1981) Cancer Bull. 33:278. These "blocking" factors can be removed from sera of tumor-bearers by absorption to Staphlococcus aureus, Cowan I cells which contain protein A, and thus allow cell-mediated tumor cell toxicity to proceed in in vitro test systems. See Steele, G., Ankerst, J., and Sjogren, H. (1974) Int. J. Cancer 14:83. Protein A also activates polyclonal antibody synthesis independent of its IgG binding activity. See Sjodahl, J. and Moller, G (1979) Scand. J. Immunol. 10:593.
Extensive testing of protein A as an anticancer agent has been inhibited by the high cost of the material and by the presence of impurities in some protein A preparations. Should the cost of protein A preparations be significantly reduced and the purity improved, then further clinical testing of protein A for anticancer uses would proceed more rapidly.